title: Effects of different types of anesthetic agents on cellular protein kinase C-γ dynamics in mouse brain.
abstract: OBJECTIVE
  Although protein kinase C-γ (PKC-γ) is a target for the effects of volatile anesthetics, the molecular mechanisms of the kinase function during their action remain unclear. We examined the effects of different types of anesthetics on PKC-γ knockout mice. Furthermore, we investigated the dynamics of the kinase in brain cells obtained from mice anesthetized with these anesthetics.
  
  
  METHODS
  We measured the required times for loss of righting reflex (rtfLORR) after administration of isoflurane, sevoflurane, or propofol on PKC-γ knockout mice and compared the times with those of wild-type mice. We also used immunoblotting to investigate the intracellular distribution of PKC-γ and phosphorylated PKC-γ (p-PKC-γ) in brain cell fractions obtained from wild-type mice during the loss of righting reflex induced by these anesthetics.
  
  
  RESULTS
  Isoflurane (2.6%) and sevoflurane (3.4%) used at twice the minimum alveolar concentration significantly prolonged the rtfLORRs in PKC-γ knockout mice compared to those in wild-type mice. On the other hand, no significant difference was observed between knockout and wild-type mice treated with propofol (200 mg/kg). Examination of the cellular fractions isolated from volatile anesthetic-treated mouse brains showed that PKC-γ was significantly decreased in the synaptic membrane fraction (P2), whereas p-PKC-γ was significantly increased in P2. There was no significant change in the supernatant fraction (S). In propofol-treated mice, PKC-γ and p-PKC-γ showed no significant changes in P2 or S.
  
  
  CONCLUSIONS
  Our results provide new evidence to support the possibility of the involvement of PKC-γ in the actions of volatile anesthetics.
authors.affiliation: Department of Anesthesiology, Tokyo Medical University Hospital, Tokyo, Japan. a-takeda @ tokyo-med.ac.jp
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Miyashita
authors.forename: Takeo
authors.initials: T
authors.lastname: Nagura
authors.forename: Shusuke
authors.initials: S
authors.lastname: Sekine
authors.forename: Michihiro
authors.initials: M
authors.lastname: Murozono
authors.forename: Shohei
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchino
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; C087857:protein kinase C gamma; D011493:Protein Kinase C